OC 20.4 - Preoperative DOAC Levels are Associated with Postoperative Bleeding and Effects are Mediated by Thrombin Generation Parameters - [SONAR]: A Nested Case-Control Study and Causal Mediation Analysis

Sunday, June 23, 2024

15:30 – 15:45 ICT

Room: Plenary Hall

Presenting Author(s)

Joseph R. Shaw, MD, MSc, FRCPC

Hematologist
The Ottawa Hospital
Ottawa, Ontario, Canada

Co-Author(s)

NL

Na Li

Assistant Professor
University of Calgary
Calgary, Alberta, Canada
MG

Matthieu Grussé

Laboratory Scientist
Diagnostica Stago
Gennevilliers, Ile-de-France, France
Patrick Van Dreden, PhD

Clinical Research Manager
Diagnostica Stago
Gennevilliers, Ile-de-France, France
MS

Melanie St John

Research Coordinator
McMaster University
Hamilton, Ontario, Canada
JD

Joanne Duncan

Research Coordinator
McMaster University
Hamilton, Ontario, Canada
AS

Alex Spyropoulos

Professor
The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
New York, New York, United States
Sam Schulman

Hematologist
McMaster University
Hamilton, Ontario, Canada
Jerrold H. Levy, MD

Professor of Anesthesiology, Critical Care, and Surgery (Cardiac)
Duke University Medical Center
Durham, North Carolina, United States
Marc Carrier, MD

Professor
Department of Medicine, University of Ottawa at the The Ottawa Hospital
Ottawa, Ontario, Canada
James Douketis

Professor of Medicine
McMaster University
Hamilton, Ontario, Canada

Background: The DOAC concentration threshold above which a clinical impact on surgical hemostasis starts to occur is unknown. Thrombin generation assays (TGAs) can provide a comprehensive measure of the coagulation phenotype.

Aims: Determine whether preoperative DOAC levels are associated with postoperative bleeding, and whether this is mediated by altered thrombin generation.

Methods: Nested case-control study using preoperative samples from apixaban/rivaroxaban-treated atrial fibrillation patients from the prospective perioperative PAUSE study. Cases were defined as major bleeding or clinically relevant non-major bleeding by postoperative day 10; controls were participants without bleeding. Cases/controls were matched on procedural bleed risk and study site using propensity scores and optimal matching at a 1:10 ratio without replacement. DOAC plasma levels were measured using calibrated anti-Xa assays; DOAC levels ≤ 19 ng/mL were imputed using a log-normal distribution. TGA parameters were measured using Calibrated Automated Thrombography (5pM tissue factor). Analyses were guided by a predefined conceptual framework and a directed acyclic graph. We used multivariable conditional logistic regression and quasi-Bayesian Monte Carlo causal mediation analyses to evaluate the relationship between residual DOAC levels, TGA parameters and postoperative bleeding.

Results: Characteristics and DOAC levels according to case/control status are shown in Table 1. DOAC levels were higher among cases compared to controls (p = 0.03). Stronger correlations between TGA parameters and residual DOAC levels were observed in cases compared to controls (Figure 1). Except for ETP (p = 0.09), each TGA parameter (LT, TTP, peak, mVRI) was significantly associated with postoperative bleeding (p < 0.05). These findings persisted after multivariable adjustment (Figure 1). The effect of DOAC levels on bleeding was mediated by altered TGA parameters (Figure 1, LT, TTP, peak, mVRI; p < 0.05).

Conclusion(s): Residual DOAC levels are associated with postoperative bleeding. This effect is mediated by the impact of DOAC levels on thrombin generation.